In the medical industry, there is often a need for a laboratory technician, e.g., a cytologist or other user, to review a cytological specimen for the presence of specified cell types. A typical cytological technique is a “Pap smear” test, which involves scraping cells from a woman's cervix and analyzing the cells in order to detect the presence of abnormal cells, a precursor to the onset of cervical cancer. Cytological techniques are also used to detect abnormal cells and diseases in other parts of the human body.
Acquired cytological samples are often placed in solution and subsequently collected and transferred to a glass slide for viewing under magnification. Fixative and staining solutions are typically applied to cells on the glass slide, often called a cell smear, for facilitating examination and for preserving the specimen for archival purposes. Prepared specimens are examined using a microscope, such as the microscope 100 generally illustrated in FIGS. 1A-B, which includes a stage 110 having a surface 112 that supports a specimen slide 200 having a biological specimen 202 (e.g., as shown in FIG. 2).
One or more control knobs are provided to allow the user to move the stage 110. As shown in FIGS. 1A-B, the microscope 100 may include a coaxial control knob 120 including a first knob 121 for moving the stage 110 in one direction (e.g., x direction) and a second knob 122 coaxial with the first knob 121 for moving the stage 110 in a different direction (e.g., y direction). A light source 130, such as a tungsten-halogen light source, is positioned below the stage 110 to illuminate the specimen 202. Objective lenses 140 form a magnified image of the specimen 202, and a cytologist may view the magnified image through an ocular lens 150. Focus adjustments are made using a focus control 160, which may include coaxial focus knobs 161, 162 (e.g., for coarse and fine focus), which move the stage 110 vertically (e.g., z direction). Further aspects of microscope components are described in U.S. Publication No. 2007/0139638 A1, the contents of which are incorporated herein by reference.
Machine vision devices and automated systems have also been utilized to acquire and analyze images of biological specimens. One known automated system 300, shown in FIG. 3, includes an automated imaging microscope or station 310, a processing server 320, and an automated review station 330.
The imaging station 310 includes a camera 312 for acquiring images of the specimen 202 viewed through an imaging microscope 316. With further reference to FIG. 4, the motorized stage 314 may include, or be operably coupled to, a stage control component or module 400 that includes one or more motors 402 and associated electronic components such as a processor 404 and memory 406, which are used to control the motors 402 and the position of the stage 314 and slide 200 thereon. Referring again to FIG. 3, image data 318 generated by the camera 312 is provided to the server 320 that includes one or more processors 321-323 (generally referred to as processor 321) and memory 324 for processing image data 318 and storing results that are provided to the review station 330.
In some automated screening systems, the processor 321 delineates between normal and abnormal (or suspicious) biological material within each specimen 202. That is, the processor 321 uses diagnostic information to determine the most pertinent biological objects and their locations (e.g., x-y coordinates) on the slide 200. In one system, the server 320 processes image data 318 to identify “objects of interest” (OOIs) in the image data 318. OOIs may take the form of individual cells and cell clusters of the specimen 202. One or more OOIs can be organized within a defined boundary or fields of view of Fields of Interest (FOI), which may be defined by various geometries to include different numbers of OOIs. FOIs may be identified based on (x,y) coordinates. One known automated system identifies 22 FOIs, or 22 sets of (x,y) coordinates. Further aspects of OOIs and FOIs are described in U.S. Pat. No. 7,083,106 and U.S. Publication No. 2004/0254738 A1, the contents of which are incorporated herein by reference.
The processor 321 may be configured to rank identified OOIs, e.g., based on the degree to which certain cells or objects are at risk of having an abnormal condition such as malignancy or pre-malignancy. For example, a processor 321 may evaluate OOIs for their nuclear integrated or average optical density, and rank the OOIs according to optical density values. The OOI and FOI coordinate information may be stored for subsequent processing, review or analysis using the review station 330.
When a cytologist reviews a slide 200 using a review microscope 336 and motorized stage 334, the OII/FOI location information is provided to the review microscope 336, which automatically steps through the previously identified FOIs to present OOIs to the cytologist. In one automated system, the review station 330 includes a mouse-like joystick that is used to navigate the slide 200. For example, one system includes “NEXT” and “PREVIOUS” buttons that are used to navigate the next FOI and the previous FOI.
During specimen review, if the cytologist does not identify any suspicious cells, then that slide is considered normal. In this case, it is not necessary to scan the entire cell spot 202. However, if the cytologist identifies suspicious cells or OOIs within a FOI, the cytologist can electronically mark those OOIs by pressing a “MARK” button, and must scan the entire specimen or cell spot 202 before completing slide review.
FIG. 5 shows one manner in which the entire cell spot 202 may be scanned using a serpentine scan pattern. In the illustrated example, the scan starts at the beginning 502a (generally referred to as beginning 502) of a first scan line or chord 500a (generally referred to as “scan line 500”), traverses across a first portion of the cell spot 202 at certain positions 510 (represented as dots) on the first scan line 500a (e.g., moving left to right in the illustrated example), and beyond the cell spot 202 boundary 204 (to ensure that the entire length or width of the cell spot 202 is scanned) to the end 503a (generally referred to as end 503) of the first scan line 500a. The automated system indexes 520a down to the second or next scan line 500b such that a second portion of the cell spot 202 may be scanned (e.g., right to left) from the beginning 502b to the end 503b of that scan line 502b, at which point it is indexed 520b again to the beginning 502c of the next scan line 500c, and so on, to scan 100% of the cell spot 202.
For purposes of scanning, known automated systems include a motorized stage 334 that positions the cell spot 202 for scanning and review by the cytologist. In a first scan mode, the motorized stage 334 and slide 200 move continuously along a pre-determined scan line 500 (e.g., as shown in FIG. 5), in a manner similar to a slow moving picture. In a second scan mode, the motorized stage 334 is controlled to move the slide 200 to positions 510 on a scan line 500, and pauses at each of position 520 for a pre-determined amount of time before moving to the next position 510, pausing again, moving again, and so one for each position 510 on each scan line 500. In a third scan mode, the stage 334 and slide 200 are moved to fixed positions 510 on a scan line 500 and remain at that position 510 until the user presses a button (e.g., the “NEXT” button used for review control), to move to the next position 510 on a scan line 500.
While automated scanning modes have been used effectively, they have a number of limitations and restrictions and can be improved. Significantly, they provide very limited, if any, user control or input over the scanning parameters. For example, in the first mode mentioned above, the stage and slide move continuously, and only the speed at which the stage and slide are moved can be adjusted using a joystick. In the second scan mode described above, the scan proceeds regardless of the desire or input of the user, and in the third scan mode, the control by the user is limited to pressing a button to advance to the next position.
Thus, certain scan modes of known automated screening systems do not permit the user to select when to stop or pause the scan, change scan directions, and/or move the scan position to view a different portion of the specimen that is not on the current scan path. Moreover, in certain known systems, a user may not be able to stop or pause at a particular position for a desired amount of time but instead is moved onto the next position if too much time has passed. Further, known systems do not provide control adjustments that can be made on-the-fly. Additionally, in certain known systems, scanning progresses in strict ordered and forward manner such that scanning is advanced. Thus, known systems are unidirectional and do not permit users to go back and review a previously reviewed portion. Known automated scanning systems, therefore, provide limited control and flexibility.
These scanning control restrictions may be so limiting and inconvenient that a user may be required to employ a separate conventional manual microscope to review a selected portion of a specimen.